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Biomedical subjects

D C Anderson

Publications and source records attributed to D C Anderson.

At least 145 records · Page 8Linked to original sources
PubMed1994

A prospective study of the prevalence of clear-cut endocrine disorders and polycystic ovaries in 350 patients presenting with hirsutism or androgenic alopecia.

OBJECTIVE: To determine the frequency of polycystic ovaries (PCO) on ultrasound and the incidence of clearcut endocrine disorders leading to virilization in patients complaining of hirsutism or androgenic alopecia. The major purpose was to determine a coherent policy for the routine biochemical assessment of such women. DESIGN: A prospective study of women attending a joint skin/endocrine clinic complaining of these problems. PATIENTS: Three hundred and fifty consecutive women with hirsutism and/or androgenic alopecia were assessed. MEASUREMENTS: Baseline endocrine screens were conducted on two occasions and included measurement of serum testosterone, androstenedione, dehydroepiandrosterone sulphate, sex hormone binding globulin, LH, FSH, 17-hydroxyprogesterone and PRL. The ovaries were visualized by high-resolution pelvic ultrasound scanning. RESULTS: Eight women were identified with relevant endocrine disorders; of these, one was acromegalic and one had a microprolactinoma--in both cases the association may have been fortuitous. Three had clear-cut 21-hydroxylase deficiency, one a rare hepatic enzyme deficiency (11-reductase), one a virilizing adrenal carcinoma and one a Leydig cell tumour. The latter six cases all had persistently elevated levels of serum testosterone (> 5 nmol/l). In all, 13 women had baseline testosterone levels in excess of 5 nmol/l. Polycystic ovaries were present in 81% of the cases who had erratic cycles and 52% of those with regular cycles; PCO were present in two of the women with 21-hydroxylase deficiency and in the woman with 11-oxoreductase deficiency. The Leydig cell tumour (1.2 cm diameter) was not detected on ultrasound or CT scan. CONCLUSIONS: For the exclusion of enzyme deficiencies and virilizing tumours clinical assessment and a single serum testosterone measurement will suffice.

Adult↗
PubMed1994

Molecular mechanisms involved in superoxide-induced leukocyte-endothelial cell interactions in vivo.

Intravital microscopy was used to monitor leukocyte adherence, flux, rolling velocity, and number of rolling leukocytes (flux/velocity) in venules 25-40 microns in diameter. The superoxide-generating system, hypoxanthine and xanthine oxidase (HX/XO), was infused into the mesenteric circulation in untreated animals or in animals pretreated with either catalase (a hydrogen peroxide scavenger), WEB-2086 [a platelet-activating factor (PAF) receptor antagonist], or monoclonal antibodies directed against adhesion molecules CD18 (CL26) or P-selectin (PB1.3). HX/XO infusion caused a decrease in leukocyte rolling velocity and an increase in the number of rolling and adherent leukocytes. WEB-2086 prevented the increase in leukocyte adhesion and markedly increased leukocyte rolling velocity. PB1.3 abolished the HX/XO-associated rise in the flux of rolling leukocytes and proportionally decreased the number of adherent leukocytes. CL26 abolished HX/XO-induced leukocyte adhesion and also reduced the number of rolling leukocytes. In conclusion, P-selectin mediates the increased leukocyte flux induced by superoxide, whereas PAF and CD18 modulate leukocyte adhesion. PAF also reduces leukocyte rolling velocity, possibly as a result of CD18, but not P-selectin.

Animals↗
PubMed1994

Molecular determinants of lipid mediator-induced leukocyte adherence and emigration in rat mesenteric venules.

The objective of this study was to identify the molecular determinants of leukocyte rolling, adherence, and emigration elicited in postcapillary venules by the lipid mediators leukotriene B4 (LTB4) or platelet-activating factor (PAF). Leukocyte-endothelial cell adhesion and shear rate were monitored in rat mesenteric venules during superfusion with either LTB4 or PAF in the presence or absence of monoclonal antibodies (MAbs) directed against either leukocyte (CD18, CD11b) or endothelial cell [intercellular adhesion molecule 1 (ICAM-1), E-selectin, P-selectin] adhesion glycoproteins. In untreated animals and in animals receiving a nonbinding control MAb, LTB4 and PAF increased the number of both adherent (8- and 4-fold, respectively) and emigrated (14- and 8-fold, respectively) leukocytes, while reducing leukocyte rolling velocity (36 and 33%, respectively). The LTB4- and PAF-induced leukocyte adherence and emigration were significantly attenuated by pretreatment with MAbs directed against CD18, CD11b, ICAM-1, and E-selectin, but not P-selectin. The reduction in leukocyte rolling velocity induced by LTB4 was not affected by any of the MAbs; however, both P- and E-selectin MAbs significantly attenuated the reduction in leukocyte rolling velocity elicited by PAF. The results of this study indicate that the leukocyte adherence and emigration induced by both LTB4 and PAF are mediated by CD11b/CD18 on leukocytes and by ICAM-1 and E-selectin on endothelial cells. The molecular determinant of leukocyte rolling appears to be mediator specific, with the selectins mediating the rolling elicited by PAF.

Animals↗
PubMed1994

Molecular determinants of reperfusion-induced leukocyte adhesion and vascular protein leakage.

The adherence and emigration of leukocytes have been implicated as a rate-limiting step in the microvascular dysfunction associated with reperfusion of ischemic tissues. The objective of the present study was to define the relation between leukocyte-endothelial cell adhesion and albumin leakage in rat mesenteric venules exposed to ischemia and reperfusion (I/R). Leukocyte adherence and emigration as well as albumin extravasation were monitored in single post-capillary venules using intravital fluorescence microscopy. Ischemia (0, 10, 15, or 20 minutes) was induced by complete occlusion of the superior mesenteric artery, and all parameters were monitored for 30 minutes after reperfusion. The magnitude of the leukocyte adherence and emigration and albumin leakage elicited by I/R was positively correlated with the duration of ischemia. The albumin leakage response was also highly correlated with the number of adherent and emigrated leukocytes. Monoclonal antibodies against the adhesion glycoproteins CD18, CD11b, intercellular adhesion molecule-1 (ICAM-1) (at 10 and 30 minutes), and L-selectin (at 10 minutes), but not P- or E-selectin, reduced I/R-induced leukocyte adherence and emigration as well as albumin leakage. Platelet-leukocyte aggregates were formed in postischemic venules; the number of aggregates was reduced by antibodies against P-selectin, CD11b, CD18, and ICAM-1, but not E- or L-selectin. These results indicate that reperfusion-induced albumin leakage is tightly coupled to the adherence and emigration of leukocytes in postcapillary venules. This adhesion-dependent injury response is primarily mediated by CD11b/CD18 on activated neutrophils and ICAM-1 on venular endothelium and appears to require L-selectin-dependent leukocyte rolling.

Animals↗
PubMed1994

Identification of a novel simian parvovirus in cynomolgus monkeys with severe anemia. A paradigm of human B19 parvovirus infection.

Although human B19 parvovirus infection has been clearly associated with a number of distinct syndromes (including severe anemia, abortion, and arthritis), detailed knowledge of its pathogenesis has been hindered by the lack of a suitable animal model. We have identified a novel simian parvovirus in cynomolgus monkeys with severe anemia. Sequencing of a 723-bp fragment of cloned viral DNA extracted from serum revealed that the simian parvovirus has 65% homology at the DNA level with the human B19 parvovirus but little homology with other known parvoviruses. Light microscopic examination of bone marrow from infected animals showed intranuclear inclusion bodies, and ultrastructural studies showed viral arrays characteristic of parvoviruses. Another striking feature was the presence of marked dyserythropoiesis in cells of the erythroid lineage, raising the possibility that B19 parvovirus infection may underlie related dyserythropoietic syndromes in human beings. Affected animals had concurrent infection with the immunosuppressive type D simian retrovirus, analogous to HIV patients who develop severe anemia because of infection with B19 parvovirus. The remarkable similarities between the simian and B19 parvoviruses suggest that experimentally infected cynomolgus monkeys may serve as a useful animal model of human B19 infection.

Amino Acid Sequence↗
PubMed1994

Clostridium difficile toxin A-induced microvascular dysfunction. Role of histamine.

Clostridium difficile toxin A (Tx-A) mediates secretion and inflammation in experimental enterocolitis. Intravital video microscopy was used to define the mechanisms that underlie the inflammatory reactions elicited by direct exposure of the microvasculature to Tx-A. Leukocyte adherence and emigration, leukocyte-platelet aggregation, and extravasation of FITC-albumin were monitored in rat mesenteric venules exposed to Tx-A. Significant increases in leukocyte adherence and emigration (LAE) and albumin leakage were noted within 15-30 min of Tx-A exposure. These responses were accompanied by mast cell degranulation and the formation of platelet-leukocyte aggregates. The Tx-A-induced increases in LAE and albumin leakage were significantly attenuated by pretreatment with either monoclonal antibodies (mAbs) directed against the leukocyte adhesion glycoproteins, CD11/CD18, intercellular adhesion molecule-1, and P-selectin (but not E-selectin) or with sialyl Lewis x, a counter-receptor for P-selectin. The mast cell stabilizer, lodoxamide, an H1- (but not an H2-) receptor antagonist, and diamine oxidase (histaminase) were also effective in reducing the LAE and albumin leakage elicited by Tx-A. The platelet-leukocyte aggregation response was blunted by an mAb against P-selectin, sialyl Lewis x, and the H1-receptor antagonist. These observations indicate that Tx-A induces a leukocyte-dependent leakage of albumin from postcapillary venules. Mast cell-derived histamine appears to mediate at least part of the leukocyte-endothelial cell adhesion and platelet-leukocyte aggregation by engaging H1-receptors on endothelial cells and platelets to increase the expression of P-selectin. The adhesion glycoproteins CD11/CD18 and intercellular adhesion molecule-1 also contribute to the inflammatory responses elicited by toxin A.

Animals↗
PubMed1994

Chest radiography in patients with early stage prostatic carcinoma. Effect on treatment planning and cost analysis.

STUDY OBJECTIVE: An evaluation of the impact of routine preoperative chest radiographs was retrospectively undertaken in a pilot group of 292 patients with prostatic carcinoma who were part of a prospective study of prostate specific antigen screening for prostate carcinoma. DESIGN: Retrospective. SETTING: Hospital-based outpatients. PATIENTS AND PARTICIPANTS: A cost-effectiveness model was used to assess the value of routine chest radiography in this patient population. Chest radiography findings were categorized into four groups based on follow-up and impact. MEASUREMENTS AND RESULTS: Forty-three patients (15 percent) had a total of 45 positive findings on their chest radiographs. No patient had intrathoracic metastases from prostatic carcinoma. Only two patients (both with unsuspected second neoplasms) had findings that impacted on their treatment and one avoided retropubic radical prostatectomy. Total cost was $2,000 (based on Medicare reimbursement), or $14,000 (based on physician and hospital charges). CONCLUSION: Although benefit is small in terms of number of patients affected, clinical impact, in the two patients with significant findings, was great. Although cost-effectiveness cannot be confirmed on the basis of this series, further evaluation of its utility for this application should be undertaken.

Aged↗
PubMed1994

Life cycle evaluation of five biological types of beef cattle in a cow-calf range production system: I. Model development.

Data collected during a 10-yr study at the Northern Agricultural Research Center (NARC), Havre, MT were used in construction of a simulation model to evaluate production systems using different breed groups. Five dam breed groups, straightbred Hereford (HH), 50% Angus-50% Hereford (AH), 25% Simmental-75% Hereford (1S3H), 50% Simmental-50% Hereford (1S1H), and 75% Simmental-25% Hereford (3S1H), were studied. The simulated system was a northern range cow-calf production system with spring calving and fall weaning. Replacement heifers were purchased and all calves were marketed at weaning. All nonpregnant females were sold in the fall. Statistical analyses of the data yielded input values (least squares means for breed group x age x sex subclasses) for cow and calf weights, pregnancy rate, dystocia, and calf survival. Pregnancy, dystocia, calf survival, calf weights, and cow weights were simulated stochastically. Energy requirements for maintenance, growth, gestation, and lactation were predicted from equations adapted from the literature based on body weight, frame size, sex, and breed group. Economic inputs and outputs were computed by accounting for variable input expenses and output revenues associated with animal performance and fixed costs associated with range management. Simulated measures of system performance included measures of energy conversion, break-even prices, and profit.

Animal Feed↗
PubMed1994

Life cycle evaluation of five biological types of beef cattle in a cow-calf range production system: II. Biological and economic performance.

Results from a 10-yr study of five dam breed groups in a range beef production system were used as inputs to a simulation model to evaluate life cycle biological and economic performance. Dam breed groups were straightbred Herefords (HH), Angus-Hereford and Simmental-Hereford F1 crosses (AH and 1S1H), 75% Hereford-25% Simmental (1S3H), and 25% Hereford-75%. Simmental (3S1H). Biological measures were number of lifetime matings, calves weaned and kilograms of calf weight sold per cow exposed, and metabolizable energy (ME) consumed per kilogram of calf weight sold and per kilogram of total weight sold. Simulated economic measures were break-even steer prices, total production costs, net profit per cow exposed, and net profit for a ranch of fixed size. The HH and 3S1H dams consumed the least ME per kilogram of total weight sold yet had the highest steer break-even prices and lowest profits. The F1 dams yielded consistently higher profits than other dam breed groups. Breed group rankings were not sensitive to prices paid for hay or calf prices relative to cow prices. Regression techniques were used to estimate maternal heterosis and maternal breed substitution effects from the simulated data. Maternal heterosis effects were large and highly significant for all measures of system performance and were desirable for all traits except ME/kilogram of total weight sold. Maternal heterosis for net profit was nearly $70.cow-1.yr-1 and $20,400/yr for a ranch of fixed size (2,700 AUM range forage). Maternal breed substitution effects were generally much smaller than heterosis effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1994

Encephalomyelitis due to a Sarcocystis neurona-like protozoan in a rhesus monkey (Macaca mulatta) infected with simian immunodeficiency virus.

A captive-born rhesus monkey (Macaca mulatta) experimentally infected with simian immunodeficiency virus developed neurologic abnormalities approximately seven months postinoculation. A chronic necrotizing encephalomyelitis with intralesional protozoal schizonts was diagnosed histologically. The protozoa was identified as Sarcocystis neurona based on its morphologic characteristics by light and electron microscopic examination, the developmental stages of the schizonts, and positive staining with antisera against Sarcocystis cruzi by immunocytochemical techniques. Although S. neurona may be confused with Toxoplasma gondii by light microscopy, the former lacks rhoptries, is in direct contact with the host cell cytoplasm, and divides by endopolygeny. Sarcocystis neurona has recently been identified as an etiologic agent of encephalomyelitis in horses, raccoons, and mink.

Animals↗
PubMed1994

Role of selectins in local and remote tissue injury following ischemia and reperfusion.

Ischemia (4-hour) followed by reperfusion (4-hour) of rat hind limbs results in local injury as well as remote (lung) injury. It has recently been shown that injury in this model is neutrophil- and cytokine-dependent and requires the beta 2 integrin adhesion molecules CD11a/CD18 and CD11b/CD18. The role of selectins in events leading to injury (as determined by leakage of albumin and by hemorrhage) was assessed either through the use of blocking antibodies to L-, E- or P-selectins or by the use of oligosaccharides that are reactive with selectins. Lung injury was found to be L- and E-selectin-dependent. When the ischemia and reperfusion times were reduced, lung injury was also found to be P-selectin dependent. In the case of hind limb injury involving the crural muscle mass, injury was L-selectin-dependent but independent of requirements for P- and E-selectin. Injury in both organs was blocked by the infusion of sialylated Lewis pentasaccharide, whereas sialyl-N-acetyllactosamine pentasaccharide failed to protect against injury. In general, when selectin-blocking approaches were protective, there were parallel reductions in tissue content of myeloperoxidase. These data underscore the role of selectins in ischemia-reperfusion injury and suggest that selectin requirements may vary with the vascular bed under study.

Animals↗
PubMed1994

Role of leukocyte adhesion molecules in lung and dermal vascular injury after thermal trauma of skin.

Acute second degree thermal injury of rat skin involving 25 to 30% total body surface of anesthetized rats results at 4 hours in evidence of vascular injury both locally (in skin) and remotely (involving lung). The neutrophil dependency for both types of injury has now been established. Monoclonal antibodies to various adhesion molecules have been used to define the requirements for these molecules in the development of vascular injury. In dermal vascular injury, a requirement for Mac-1 (CD11b/CD18) but not for leukocyte function-associated antigen-1 (LFA-1, CD11a/CD18) has been established. In this model requirements have also been demonstrated for intercellular adhesion molecule-1 (ICAM-1) and E- and L-selectin but not for very late arising antigen-4 (VLA-4) or P-selectin. With respect to lung vascular injury, dual requirements for both leukocyte function-associated antigen-1 and Mac-1 were found as well as for ICAM-1 and E- and L-selectin but not for VLA-4 and P-selectin. In the lung, there was a close correlation between neutrophil content of the tissue (as assessed by myeloperoxidase) and the effects of protective interventions (directed against blocking of adhesion molecules). These data emphasize the roles of beta 2 integrins, selectins (L and E), and ICAM-1 in events that lead to neutrophil-mediated vascular injury of dermis and lung after thermal trauma to skin.

Animals↗
PubMed1993

Beta 2-integrin and L-selectin are obligatory receptors in neutrophil aggregation.

We have recently found that antibodies to L-selectin, the homing receptor on neutrophils, are as effective as those to beta 2-integrin at blocking formyl peptide-stimulated aggregation. Therefore, we investigated the requirements for expression of L-selectin and beta 2-integrin on adjacent cells during aggregation. Fluorescence flow cytometry allowed characterization of aggregates on the basis of size and color, as well as antibody binding to these two adhesive molecules. Formyl peptide-stimulated aggregate formation was measured for individual populations fluorescently labeled red (LDS-751) or green (CD44-FITC), and interpopulation red-green cell conjugates. Blocking either the beta 2-integrin or L-selectin adhesive epitope with monoclonal antibody on individual cell populations resulted in an approximately 50% reduction in two-color aggregation as compared with that in unblocked samples. Shedding the L-selectin on a cell population by preincubation with complexes of lipopolysaccharide and its plasma membrane binding protein also decreased aggregation to a control population by approximately 50%. We examined the aggregation of neutrophils from patients genetically deficient in beta 2-integrin and clinically leukocyte adhesion deficient (LAD). LAD adhesion to normal neutrophils was dependent on the expression of L-selectin on LAD cells and beta 2-integrin on normal cells. Thus, the minimum requirement for adhesion between two mixed populations of neutrophils was that one population expressed the beta 2-integrin and the other expressed the L-selectin adhesive epitope.

Animals↗
PubMed1993

Tumor cell retention of antibody Fab fragments is enhanced by an attached HIV TAT protein-derived peptide.

Two peptide analogs of the 37-62 sequence region of the HIV TAT protein bind tightly to the surface of A431 breast carcinoma cells. After conjugation to either of two poorly internalized anti-tumor antibody Fab fragments, the analogs enhanced the in vitro cell surface retention and internalization of the Fab fragments to the level of the whole antibodies. This was at the expense of some binding specificity in the case of 1.6 peptides/NRLU-10 Fab, but not in the case of 1.1 peptides/Fab. Enhanced retention may occur by enhanced bivalent binding of the Fab fragments. The internalized fraction of free peptide, but not of the Fab conjugates, is enhanced by chloroquine. The conjugates which were less specific for tumor cell binding may be useful for enhanced retention/internalization of specifically acting agents, for use at specific sites of injection, or against pre-separated target cell populations, while the more specific conjugate may be of interest for further development.

Amino Acid Sequence↗
PubMed1993

Role of beta 1, beta 2 integrins and ICAM-1 in lung injury after deposition of IgG and IgA immune complexes.

After intrapulmonary deposition of IgG or IgA immune complexes, injury has been recently shown to be CD18-dependent in both cases and E-selection-dependent only in the former case. In our studies further evaluation of the requirements for beta 1 and beta 2 integrins and intercellular adhesion molecule-1 (ICAM-1) has been undertaken. In the IgG immune complex model, which is neutrophil dependent, anti-CD11a reduced injury (as measured by changes in permeability and hemorrhage) by 61 and 43%, respectively, whereas a newly developed anti-CD11b produced minimal protection (16 and 19%, respectively). Treatment of rats with increasing doses (1.5- and 3.0-fold) of antibody to rat CD11b failed to demonstrate additional protective effects in this model of injury. Anti-ICAM-1 reduced the parameters of injury by 61 and 78%, respectively, while anti-VLA-4 reduced the injury parameters by 40 and 35%, respectively. There were reductions in lung content of myeloperoxidase, roughly corresponding to the protective effects of the interventions. In the IgA immune complex model of injury, in which lung macrophages appear to be the effector cells, anti-CD11a reduced the injury parameters (permeability and hemorrhage) by 36 and 33%, respectively, whereas anti-CD11b reduced the parameters of injury by 63 and 67%, respectively. In this model, anti-ICAM-1 reduced the parameters of injury by 61 and 56%, respectively, while anti-VLA-4 reduced the parameters by 77 and 62%, respectively. The cell content of bronchoalveolar lavage fluids revealed changes that have been shown to reflect protective interventions in both models of immune complex-induced injury. These findings suggest that, in IgG and IgA immune complex models of lung injury, both VLA-4 and ICAM-1 are required, although lymphocyte function-associated Ag-1 is the predominant beta 2 integrin requirement in the IgG immune complex-induced model of injury and Mac-1 is the predominant requirement for IgA immune complex-induced lung injury. Thus, engagement in the lung of adhesion molecules in a manner leading to injury depends on the nature of the inflammatory stimulus and the type of phagocytic cells involved in the development of injury.

Animals↗